Background: Central nervous system tumors which constitute 1-2% of all tumors pose diagnostic challenges because tumors of varying histogenesis show divergent differentiation and overlap in morphological features. In problematic cases, immunohistochemistry is done in addition to the routine histopathologic examination to overcome the diagnostic difficulties, since an accurate histologic diagnosis helps in predicting the clinical outcome of various brain tumors. Materials and Methods: This study was carried out on a prospective basis in our institution from January 2009 to March 2012. During this period, a total of 246 neurosurgical specimens were received among which 118 brain tumors were diagnosed based on examination of Hematoxylin and Eosin stained sections of formalin-fixed and paraffin-embedded biopsy specimens. Immunohistochemical markers were applied in selective cases for an accurate diagnosis. Results: In adults, astrocytomas occurred most frequently in the study, followed by meningiomas, nerve sheath tumors, metastatic deposits, glioblastomas, and gliosarcomas. Primitive neurectodermal tumors occurred frequently in children. Other rare tumors included lymphomas and mesenchymal tumors. Age and sex incidence and anatomic distribution of various tumors were studied. Grading of the tumors was done as per the revised World Health Organization criteria. The results of immunohistochemical study in selective cases were analyzed. Conclusion: This study highlights the utility of immunohistochemistry as an adjunct in the histologic diagnosis of brain tumors in difficult cases.